Characterization of environmental determinants of cancer is an important goal for developing effective public health strategies in prevention and control of cancer. Informative epidemiological investigations of environment-cancer relationships rely on accurate, quantifiable exposure measurements. In traditional population surveys that attempt to link a substance with cancer occurrence, exposure data is often obtained indirectly in the form of questionnaires or personal interviews. The uncertainty associated with errors in exposure assessment has obscured or limited identification of cancer etiologies. Rather than the current reliance on external dose estimation and extrapolation from high dose exposure with rodent models, sufficiently sensitive biomarkers based on DNA damage measurements could allow for a more realistic assessment of environmental risk. A broad, long-term objective of this project is to develop innovative, cost-effective, and reliable technology for quantifying exposures, especially low level exposures. Specific aims include developing highly sensitive technology for measuring minute amounts of DNA damage and to improve biomarkers for epidemiological investigations of environment-cancer relationships. The technology combines the specificity of antibodies and capillary electrophoresis separation with high sensitivity of laser induced fluorescence detection. In addition, specific DNA-recognition proteins will be used to bind with various DNA lesions for detection of a range of DNA lesions. Automated and high throughput assay formats making use of the high sensitivity technology will be explored. The sensitive DNA damage measurements will be used as potential biomarkers for exposure assessment. The technology will also be useful for monitoring DNA damage induced by anticancer agents and for studying DNA repair, which is an essential protection mechanism against cancer initiation.